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不同劑量堿性成纖維細(xì)胞生長(zhǎng)因子治療鼓膜創(chuàng)傷性穿孔的療效比較

2016-03-02 01:35樓正才陳華英吳小洪
中國(guó)全科醫(yī)學(xué) 2016年6期
關(guān)鍵詞:治療結(jié)果創(chuàng)傷

樓正才,陳華英,吳小洪

作者單位:322000 浙江省義烏市,溫州醫(yī)科大學(xué)附屬義烏醫(yī)院耳鼻咽喉科

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不同劑量堿性成纖維細(xì)胞生長(zhǎng)因子治療鼓膜創(chuàng)傷性穿孔的療效比較

樓正才,陳華英,吳小洪

作者單位:322000 浙江省義烏市,溫州醫(yī)科大學(xué)附屬義烏醫(yī)院耳鼻咽喉科

【摘要】目的比較高劑量、低劑量堿性成纖維細(xì)胞生長(zhǎng)因子(bFGF)治療鼓膜創(chuàng)傷性穿孔的療效。方法選取2012年7月—2014年2月溫州醫(yī)科大學(xué)附屬義烏醫(yī)院耳鼻咽喉科門(mén)、急診收治的鼓膜創(chuàng)傷性穿孔患者168例為研究對(duì)象,根據(jù)初次接診時(shí)鼓膜創(chuàng)傷性穿孔大小及接診時(shí)間的先后順序隨機(jī)分為低劑量組85例和高劑量組83例。低劑量組給予重組牛bFGF滴眼液滴耳,1次/d,2~3滴/次(0.10~0.15 ml);高劑量組給予重組牛bFGF滴眼液滴耳,1次/d,5~6滴/次(0.25~0.30 ml)。隨訪至鼓膜創(chuàng)傷性穿孔愈合或治療3個(gè)月后,記錄兩組患者穿孔時(shí)間、膿性耳漏發(fā)生率、愈合率及愈合時(shí)間。結(jié)果治療3個(gè)月后,168例患者中11例失訪。低劑量組與高劑量組患者穿孔時(shí)間、愈合率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。高劑量組患者膿性耳漏發(fā)生率高于低劑量組,愈合時(shí)間長(zhǎng)于低劑量組(P<0.05)。低劑量組與高劑量組中穿孔、大穿孔患者穿孔時(shí)間、愈合率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);高劑量組中穿孔、大穿孔患者膿性耳漏發(fā)生率高于低劑量組,愈合時(shí)間長(zhǎng)于低劑量組(P<0.05)。高劑量組15例繼發(fā)膿性耳漏的中穿孔患者,13例(86.7%)愈合,平均愈合時(shí)間(16.4±4.7)d;13例繼發(fā)膿性耳漏的大穿孔患者均愈合,平均愈合時(shí)間(15.1±5.3)d。結(jié)論每天持續(xù)小劑量重組牛bFGF滴眼液滴耳維持鼓膜潮濕環(huán)境足以引起鼓膜創(chuàng)傷性穿孔愈合,避免膿性耳漏;大劑量重組牛bFGF滴眼液滴耳引起的鼓膜水樣環(huán)境反而引起膿性耳漏,延長(zhǎng)愈合時(shí)間。

鼓膜創(chuàng)傷性穿孔是耳科常見(jiàn)疾病,其具有自然愈合能力,但大穿孔自然愈合率低,愈合時(shí)間需要4~12周[1-3]。為縮短愈合時(shí)間,提高患者生活質(zhì)量,許多學(xué)者采用穿孔緣修復(fù)+鼓膜成形術(shù)或貼片治療[4-6]。然而,鼓膜成形術(shù)需要麻醉且其可能造成并發(fā)癥,貼片治療只能縮短愈合時(shí)間,不能提高愈合率[4-6]。近年來(lái)研究證明,局部應(yīng)用(直接應(yīng)用或與貼片聯(lián)合應(yīng)用)堿性成纖維細(xì)胞生長(zhǎng)因子(bFGF)能縮短愈合時(shí)間,提高愈合率[7-10]。但對(duì)bFGF的使用劑量一直存在爭(zhēng)論,少數(shù)學(xué)者認(rèn)為,小劑量bFGF并不能加速鼓膜創(chuàng)傷性穿孔愈合[11],而另一些學(xué)者認(rèn)為,大劑量bFGF能加速鼓膜創(chuàng)傷性穿孔愈合,但易并發(fā)膿性耳漏、鼓膜炎和遠(yuǎn)期中耳膽脂瘤[9,11-12]。然而,未見(jiàn)直接應(yīng)用bFGF治療人類鼓膜創(chuàng)傷性穿孔最佳劑量的報(bào)道。本研究的目的是評(píng)估直接應(yīng)用bFGF治療人類鼓膜創(chuàng)傷性穿孔的較佳劑量,現(xiàn)報(bào)道如下。

1資料與方法

1.1納入與排除標(biāo)準(zhǔn)納入標(biāo)準(zhǔn):(1)掌拳擊傷、鞭炮炸傷或運(yùn)動(dòng)擊傷等引起的鼓膜創(chuàng)傷性穿孔患者;(2)年齡6歲以上,穿孔時(shí)間30 d以內(nèi);(3)鼓膜穿孔面積至少占鼓膜緊張部面積的1/8及以上,初診時(shí)無(wú)中耳感染。排除標(biāo)準(zhǔn):(1)伴嚴(yán)重眩暈;(2)外耳道或中耳有肉芽組織增生;(3)懷疑聽(tīng)骨鏈損傷;(4)化學(xué)燒傷或伴嚴(yán)重復(fù)合傷、顱底骨折。

1.2臨床資料選取2012年7月—2014年2月溫州醫(yī)科大學(xué)附屬義烏醫(yī)院耳鼻咽喉科門(mén)、急診收治的鼓膜創(chuàng)傷性穿孔患者168例為研究對(duì)象,其中男56例,女112例;年齡14~57歲,平均年齡(38.2±5.4)歲;左耳147例,右耳21例;中穿孔(鼓膜穿孔面積占鼓膜緊張部面積的1/8~1/4)101例,大穿孔(鼓膜穿孔面積占鼓膜緊張部面積的1/4以上)67例。

1.3分組根據(jù)初次接診時(shí)鼓膜創(chuàng)傷性穿孔大小及接診時(shí)間的先后順序隨機(jī)分為兩組,低劑量組85例和高劑量組83例。兩組患者性別、年齡、穿孔側(cè)別、穿孔大小及穿孔原因比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05,見(jiàn)表1)。本研究得到溫州醫(yī)科大學(xué)附屬義烏醫(yī)院醫(yī)學(xué)倫理審查委員會(huì)批準(zhǔn),所有患者簽署知情同意書(shū)。

表1低劑量組與高劑量組患者一般資料比較

Table 1Comparison of general data between low-dose group and high-dose group

組別例數(shù)性別(男/女)年齡(歲)穿孔側(cè)別(左耳/右耳)中穿孔/大穿孔穿孔原因(掌拳擊傷/鞭炮炸傷)低劑量組8531/5437.9±6.474/1151/3483/2高劑量組8325/5838.7±5.973/1050/3379/4χ2(t)值0.7620.842a0.0310.0010.742P值0.3830.4010.8610.9750.389

注:a為t值

1.4治療方法均采用1%PPI棉球清理外耳道耵聹及血痂。低劑量組給予重組牛bFGF滴眼液(珠海億勝生物制藥有限公司,批準(zhǔn)文號(hào):國(guó)藥準(zhǔn)字S19991022,規(guī)格:21 000 U/5 ml)滴耳,1次/d,2~3滴/次(0.10~0.15 ml),維持鼓膜潮濕環(huán)境但未見(jiàn)明顯水樣液體;高劑量組給予重組牛bFGF滴眼液滴耳,1次/d,5~6滴/次(0.25~0.30 ml),維持鼓膜或鼓室水樣環(huán)境。治療過(guò)程沒(méi)有采用穿孔緣修復(fù)及貼片治療。兩組患者同時(shí)口服阿莫西林克拉維酸鉀片(華北制藥股份有限公司,批準(zhǔn)文號(hào):國(guó)藥準(zhǔn)字H10920034)1周預(yù)防感染。首次治療3 d后隨訪,觀察用藥方法是否正確、有無(wú)感染,此后至少每周隨訪1次,直至鼓膜創(chuàng)傷性穿孔愈合或治療3個(gè)月后。每次隨訪時(shí)耳內(nèi)鏡檢查評(píng)估鼓膜創(chuàng)傷性穿孔大小、有無(wú)中耳感染并確認(rèn)愈合時(shí)間。

1.5觀察指標(biāo)記錄兩組患者穿孔時(shí)間、膿性耳漏發(fā)生率、愈合率及愈合時(shí)間。

2結(jié)果

治療3個(gè)月后,168例患者中11例失訪,其中低劑量組2例和高劑量組9例。低劑量組與高劑量組患者穿孔時(shí)間、愈合率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);高劑量組患者膿性耳漏發(fā)生率高于低劑量組,愈合時(shí)間長(zhǎng)于低劑量組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見(jiàn)表2)。低劑量組與高劑量組中穿孔患者穿孔時(shí)間、愈合率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);高劑量組中穿孔患者膿性耳漏發(fā)生率高于低劑量組,愈合時(shí)間長(zhǎng)于低劑量組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見(jiàn)表3)。低劑量組與高劑量組大穿孔患者穿孔時(shí)間、愈合率比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);高劑量組大穿孔患者膿性耳漏發(fā)生率高于低劑量組,愈合時(shí)間長(zhǎng)于低劑量組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見(jiàn)表4)。高劑量組15例繼發(fā)膿性耳漏的中穿孔患者,13例(86.7%)愈合,愈合時(shí)間11~30 d,平均愈合時(shí)間(16.4±4.7)d;13例繼發(fā)膿性耳漏的大穿孔患者均愈合,愈合時(shí)間9~25 d,平均愈合時(shí)間(15.1±5.3)d。低劑量組與高劑量組典型患者穿孔愈合過(guò)程見(jiàn)圖1、2(本文圖1、2彩圖見(jiàn)本刊官網(wǎng)www.chinagp.net電子期刊相應(yīng)文章附件)。

3討論

臨床研究和實(shí)驗(yàn)研究均證明,局部應(yīng)用bFGF可縮短鼓膜創(chuàng)傷性穿孔的愈合時(shí)間,提高愈合率[7-13]。本課題組前期研究也證明,與自然愈合相比,局部應(yīng)用bFGF能顯著提高愈合率和縮短愈合時(shí)間[10]。

然而,bFGF治療人類鼓膜創(chuàng)傷性穿孔的劑量一直存在爭(zhēng)議。Kanemaru等[9]和Mondain等[11]認(rèn)為,使用200 ng低劑量bFGF并未提高愈合率,然而,單劑量使用2 000 ng的bFGF雖然能提高愈合率,但可繼發(fā)鼓膜炎及表皮樣囊腫,推薦治療鼓膜創(chuàng)傷性穿孔的合適劑量為400 ng。Vrabec等[12]發(fā)現(xiàn),應(yīng)用高劑量bFGF可以遠(yuǎn)期并發(fā)中耳膽脂瘤。本研究結(jié)果顯示,不論是低劑量bFGF還是高劑量bFGF,與文獻(xiàn)報(bào)道的自然愈合相比[1-3],局部應(yīng)用bFGF可顯著縮短愈合時(shí)間。然而,本研究顯示,無(wú)論是大穿孔還是中穿孔,盡管高劑量組與低劑量組的愈合率沒(méi)有差異,但是高劑量組平均愈合時(shí)間延長(zhǎng)。這可能與高劑量bFGF能抑制鼓膜纖維層膠原蛋白合成有關(guān)。國(guó)外Lazarou等[14]和Kato等[15]發(fā)現(xiàn),在皮膚創(chuàng)傷修復(fù)中,局部持續(xù)應(yīng)用高劑量bFGF能抑制膠原蛋白合成,促進(jìn)膠原蛋白分解代謝,延長(zhǎng)創(chuàng)口愈合時(shí)間。本研究結(jié)果表明,與低劑量bFGF比較,高劑量bFGF的局部應(yīng)用增加了膿性耳漏發(fā)生率。K?licke等[16]在豚鼠的體內(nèi)外研究中發(fā)現(xiàn),局部應(yīng)用bFGF增加了創(chuàng)傷后局部感染的風(fēng)險(xiǎn),增加的感染能損傷穿孔的愈合。

表2低劑量組與高劑量組患者觀察指標(biāo)比較

Table 2Comparison of observational indexes between low-dose group and high-dose group

組別例數(shù)穿孔時(shí)間(d)膿性耳漏〔n(%)〕愈合率〔n(%)〕愈合時(shí)間(d)低劑量組834.6±2.3082(98.8) 9.6±2.7 高劑量組744.9±3.728(37.8)71(95.9)14.0±4.6χ2(t)值0.617a38.2221.2797.402aP值0.538<0.0010.258<0.001

注:a為t值

表3低劑量組與高劑量組中穿孔患者觀察指標(biāo)比較

Table 3Comparison of observational indexes of middle-size TMP patients between low-dose group and high-dose group

組別例數(shù)穿孔時(shí)間(d)膿性耳漏〔n(%)〕愈合率〔n(%)〕愈合時(shí)間(d)低劑量組523.9±2.6052(100.0) 7.3±2.2 高劑量組464.1±3.215(32.6)43(93.5)12.6±5.7χ2(t)值0.341a20.0213.4986.206aP值0.734<0.0010.061<0.001

注:a為t值

注:A~C為同一患者,分別顯示鼓膜創(chuàng)傷性穿孔4 d和治療后7、10 d;D~F為同一患者,分別顯示鼓膜創(chuàng)傷性穿孔3 d和治療后8、10 d

圖1低劑量組患者穿孔愈合過(guò)程

Figure 1Repairing process of the perforation of patients in low-dose group

注:鼓膜表面可見(jiàn)水樣液體或耳漏;A~D為同一患者,分別顯示鼓膜創(chuàng)傷性穿孔4 d和治療后3、5、8 d;E~H為同一患者,分別顯示鼓膜創(chuàng)傷性穿孔1 d和治療后3、6、10 d

圖2高劑量組患者穿孔愈合過(guò)程

Figure 2Repairing process of the perforation of patients in high-dose group

表4低劑量組與高劑量組大穿孔患者觀察指標(biāo)比較

Table 4Comparison of observational indexes of large-size TMP patients between low-dose group and high-dose group

組別例數(shù)穿孔時(shí)間(d)膿性耳漏〔n(%)〕愈合率〔n(%)〕愈合時(shí)間(d)低劑量組314.7±2.3030(96.8)11.4±3.6高劑量組285.2±3.113(46.4)28(100.0)14.7±5.9χ2(t)值0.708a18.4600.9192.560aP值0.481<0.0010.3380.010

注:a為t值

局部應(yīng)用高劑量bFGF后膿性耳漏發(fā)生率增加的原因還不是很清楚。一個(gè)可能的原因是大量的中鼓室及殘余鼓膜的水樣環(huán)境給細(xì)菌提供了良好的滋生環(huán)境;另一個(gè)可能的原因是K?licke等[16]分析,高劑量bFGF對(duì)創(chuàng)口其他生長(zhǎng)因子有毒性效應(yīng),從理論上講,bFGF不僅刺激表皮細(xì)胞和成纖維細(xì)胞的增殖,也能刺激葡萄球菌的生長(zhǎng),誘導(dǎo)細(xì)菌DNA合成。本研究中繼發(fā)膿性耳漏的13例大穿孔患者均愈合,15例繼發(fā)膿性耳漏的中穿孔患者13例愈合。此結(jié)果與既往試驗(yàn)研究類似[9-10]。既往研究表明,局部應(yīng)用bFGF能克服細(xì)菌感染誘導(dǎo)的愈合損傷[17-18]。此外,在幾個(gè)慢性鼓膜創(chuàng)傷性穿孔動(dòng)物模型的研究中發(fā)現(xiàn),感染誘導(dǎo)的急性炎癥反而能促進(jìn)慢性鼓膜創(chuàng)傷性穿孔的愈合[19-20]。本研究缺陷是缺乏自然愈合的對(duì)照組;其次,高劑量bFGF與低劑量bFGF的區(qū)分僅以鼓膜表面水樣耳漏的存在為依據(jù),事實(shí)上,觀察時(shí)間及不同患者間外耳道結(jié)構(gòu)差異均可影響bFGF劑量的評(píng)估,在未來(lái)研究中,確定bFGF治療鼓膜創(chuàng)傷性穿孔的有效客觀劑量非常重要。

總之,本研究提示,每天持續(xù)應(yīng)用小劑量bFGF維持鼓膜潮濕環(huán)境治療鼓膜創(chuàng)傷性穿孔足以產(chǎn)生治療效果,避免繼發(fā)膿性耳漏,縮短愈合時(shí)間;相反,大劑量bFGF引起的鼓膜水樣環(huán)境反而可能繼發(fā)膿性耳漏,延長(zhǎng)愈合時(shí)間。

作者貢獻(xiàn):樓正才進(jìn)行試驗(yàn)設(shè)計(jì)與實(shí)施、資料收集整理、撰寫(xiě)論文并對(duì)文章負(fù)責(zé)及審校;陳華英、吳小洪進(jìn)行資料收集及試驗(yàn)實(shí)施。

本文無(wú)利益沖突。

參考文獻(xiàn)

[1]孫秀梅,王俊霞,劉靜,等.無(wú)支架治療外傷性鼓膜穿孔57例臨床總結(jié)[J].中華耳鼻咽喉科頭頸外科雜志,2013,48(8):680-682.

[2]Lou ZC,Tang YM,Yang J.A prospective study evaluating spontaneous healing of aetiology,size and type-different groups of traumatic tympanic membrane perforation[J].Clin Otolaryngol,2011,36(5):450-460.

[3]樓正才.鼓膜外傷性穿孔人為干預(yù)及自然愈合療效觀察[J].中國(guó)耳鼻咽喉科頭頸外科雜志,2008,15(12):691-692.

[4]Sprem N,Branica S,Dawidowsky K.Tympanoplasty after war blast lesions of the eardrum:retrospective study[J].Croat Med J,2001,42(6):642-645.

[5]Xu M,Gao W,Li XY,et al.A myringoplasty healing rate and hearing outcomes comparison between traumatic tympanic membrane perforation and perforation following simple chronic suppurative otitis media[J].Chinese Journal of Otology,2013,11(1):57-59.(in Chinese)

許敏,高偉,李曉媛,等.外傷性鼓膜穿孔和單純慢性化膿性中耳炎鼓膜成形術(shù)的療效比較[J].中華耳科學(xué)雜志,2013,11(1):57-59.

[6]Lou ZC,He JG.A randomised controlled trial comparing spontaneous healing,gelfoam patching and edge-approximation plus gelfoam patching in traumatic tympanic membrane perforation with inverted or everted edges[J].Clin Otolaryngol,2011,36(3):221-226.

[7]Hakuba N,Iwanaga M,Tanaka S,et al.Basic fibroblast growth factor combined with atelocollagen for closing chronic tympanic membrane perforations in 87 patients[J].Otol Neurotol,2010,31(1):118-121.

[8]Kase K,Iwanaga T,Terakado M,et al.Influence of topical application of basic fibroblast growth factor upon inner ear[J].Otolaryngol Head Neck Surg,2008,138(4):523-527.

[9]Kanemaru S,Umeda H,Kitani Y,et al.Regenerative treatment for tympanic membrane perforation[J].Otol Neurotol,2011,32(8):1218-1223.

[10]Lou Z.Healing large traumatic eardrum perforations in humans using fibroblast growth factor applied directly or via gelfoam[J].Otol Neurotol,2012,33(9):1553-1557.

[11] Mondain M,Saffiedine S,Uziel A.Fibroblast growth factor improves the healing of experimental tympanic membrane perforations[J].Acta Otolaryngol,1991,111(2):337-341.

[12]Vrabec JT,Schwaber MK,Davidson JM,et al.Evaluation of basic fibroblast growth factor in tympanic membrane repair[J].Laryngoscope,1994,104(9):1059-1064.

[13]Fina M,Baird A,Ryan A.Direct application of basic fibroblast growth factor improves tympanic membrane perforation healing[J].Laryngoscope,1993,103(7):804-809.

[14] Lazarou SA,Efrom JE,Shaw T,et al.Fibroblast growth factor inhibits wound collange synthesis[J].Surg Forum,1989,40(3):627-629.

[15]Kato M,Jackler RK.Repair of chronic tympanic membrane perforations with fibroblast growth factor[J].Otolaryngol Head Neck Surg,1996,115(6):538-547.

[16]K?licke T,K?ller M,Frangen TM,et al.Local application of basic fibroblast growth factor increases the risk of local infection after trauma:an in-vitro and in-vivo study in rats[J].Acta Orthop,2007,78(1):63-73.

[17]Hayward P,Hokanson J,Heggers J,et al.Fibroblast growth factor reverses the bacterial retardation of wound contraction[J].Am J Surg,1992,163(3):288-293.

[18]Kuhn MA,Page L,Nguyen K,et al.Basic fibroblast growth factor in a carboxymethylcellulose vehicle reverses the bacterial retardation of wound contraction[J].Wounds,2001,13(2):73-80.

[19]Spratley J,Hellstr?m S,Eriksson PO,et al.Early structural tympanic membrane reactions to myringotomy:a study in an acute otitis media model[J].Acta Otolaryngol,2002,122(5):479-487.

[20]Spratley J,Hellstr?m S,Eriksson PO,et al.Myringotomy delays the tympanic membrane recovery in acute otitismedia:a study in the rat model[J].Laryngoscope,2002,112(8):1474-1481.

(本文編輯:陳素芳)

【關(guān)鍵詞】鼓膜穿孔;創(chuàng)傷;成纖維細(xì)胞生長(zhǎng)因子;傷口愈合;治療結(jié)果

樓正才,陳華英,吳小洪.不同劑量堿性成纖維細(xì)胞生長(zhǎng)因子治療鼓膜創(chuàng)傷性穿孔的療效比較[J].中國(guó)全科醫(yī)學(xué),2016,19(6):706-709.[www.chinagp.net]

Lou ZC,Chen HY,Wu XH.Comparison of the efficacy in the treatment of traumatic tympanic membrane perforation among different doses of basic fibroblast growth factor[J].Chinese General Practice,2016,19(6):706-709.

Comparison of the Efficacy in the Treatment of Traumatic Tympanic Membrane Perforation Among Different Doses of Basic Fibroblast Growth FactorLOUZheng-cai,CHENHua-ying,WUXiao-hong.DepartmentofOtorhinolaryngology,YiwuHospitalAffiliatedtoWenzhouMedicalUniversity,Yiwu322000,China

【Abstract】ObjectiveTo compare the efficacy in the treatment of traumatic tympanic membrane perforation(TMP) between low-dose and high-dose basic fibroblast growth factor(bFGF).MethodsEnrolled 168 TMP patients who were admitted in to the outpatient emergency unit of the Department of Otorhinolaryngology of Yiwu Hospital Affiliated to Wenzhou Medical University from July 2012 to February 2014.According to the size of TMP in the first consultation and the sequence of consultation,the patients were divided into low-dose group(n=85) and high-dose group(n=83).The low-dose group was administrated with recombinant bovine bFGF-containing eye drops into ear once per day and 2-3 drops(0.10-0.15 ml) per time;the high-dose group was administrated with recombinant bovine bFGF-containing eye drops into ear once per day and 5-6 drops(0.25-0.30 ml)per time.The follow-up was conducted until the healing of TMP or three months later,during which we recorded the injury time,the incidence of purulent otorrhea,healing rate and healing time of patients.ResultsThree months later,11 patients were lost to follow-up.The two groups were not significantly different in the injury time and healing rate(P>0.05).The high-dose group had higher incidence of purulent otorrhea and longer healing time than the low-dose group(P<0.05).The two groups were not significantly different in the injury time and healing rate of patients with middle-size TMP and large-size TMP(P>0.05);the high-dose group had higher incidence of purulent otorrhea and longer healing time of middle-size TMP patients and large-size TMP patients than the low-dose group(P<0.05).In the high-dose group,there were 15 middle-size TMP patients with secondary purulent otorrhea and 13 patients that healed with an average healing time of(16.4±4.7)d;there were 13 patients with purulent otorrhea that healed with an average healing time of(15.1±5.3)d.ConclusionThe daily administration of low-dose recombinant bovine bFGF-containing eye drops that keeps a moisture environment can induce the healing effect of tympanic membrane and avoid purulent otorrheal;high-dose recombinant bovine bFGF-containing eye drops that causes water wet environment will prolong healing time and may cause purulent otorrhea.

【Key words】Tympanic membrane perforation;Traumatic;Basic fibroblast growth factor;Wound healing;Treatment outcome

(收稿日期:2015-08-10;修回日期:2016-01-05)

【中圖分類號(hào)】R 764.29

【文獻(xiàn)標(biāo)識(shí)碼】B

doi:10.3969/j.issn.1007-9572.2016.06.017

通信作者:樓正才,322000 浙江省義烏市,溫州醫(yī)科大學(xué)附屬義烏醫(yī)院耳鼻咽喉科;E-mail:louzhengcai@126.com

·療效比較研究·

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